The Intramolecular Povarov Tool in the Construction of Fused Nitrogen-Containing Heterocycles

Nitrogen heterocycles are part of the structure of natural products and agents with important biological activity, such as antiviral, antibiotic, and antitumor drugs. For this reason, heterocyclic compounds are one of today’s most desirable synthetic targets and the Povarov reaction is a powerful synthetic tool for the construction of highly functionalized heterocyclic systems. This process involves an aromatic amine, a carbonyl compound, and an olefin or acetylene to give rise to the formation of a nitrogen-containing heterocycle. This review illustrates advances in the synthetic aspects of the intramolecular Povarov reaction for the construction of intricate nitrogen-containing polyheterocyclic compounds. This original review presents research done in this field, with references to important works by internationally relevant research groups on this current topic, covering the literature from 1992 to 2022. The intramolecular Povarov reactions are described here according to the key processes involved, using different combinations of aromatic or heteroaromatic amines, and aliphatic, aromatic, or heteroaromatic aldehydes. Some catalytic reactions promoted by transition metals are detailed, as well as the oxidative Povarov reaction and some asymmetric intramolecular Povarov processes.Financial support from the Ministerio de Ciencia, Innovación y Universidades (MCIU) (PID2021-122558OB-I00, UE), by Gobierno Vasco, Universidad del País Vasco (GV, IT1701- 22; UPV) and by Fundación Vital (VITAL21/01) is gratefully acknowledged. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Natur

Synthetic Strategies, Reactivity and Applications of 1,5-Naphthyridines

This review covers the synthesis and reactivity of 1,5-naphthyridine derivatives published in the last 18 years. These heterocycles present a significant importance in the field of medicinal chemistry because many of them exhibit a great variety of biological activities. First, the published strategies related to the synthesis of 1,5-naphthyridines are presented followed by the reactivity of these compounds with electrophilic or nucleophilic reagents, in oxidations, reductions, cross-coupling reactions, modification of side chains or formation of metal complexes. Finally, some properties and applications of these heterocycles studied during this period are examined.This research was funded by the Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI), Fondo Europeo de Desarrollo Regional (FEDER; RTI2018-101818-B-I00, UE) and by Gobierno Vasco, Universidad del País Vasco (GV, IT 992-16; UPV)

Fused 1,5-Naphthyridines: Synthetic Tools and Applications

Heterocyclic nitrogen compounds, including fused 1,5-naphthyridines, have versatile applications in the fields of synthetic organic chemistry and play an important role in the field of medicinal chemistry, as many of them have a wide range of biological activities. In this review, a wide range of synthetic protocols for the construction of this scaffold are presented. For example, Friedländer, Skraup, Semmlere-Wolff, and hetero-Diels-Alder, among others, are well known classical synthetic protocols used for the construction of the main 1,5-naphthyridine scaffold. These syntheses are classified according to the nature of the cycle fused to the 1,5-naphthyridine ring: carbocycles, nitrogen heterocycles, oxygen heterocycles, and sulphur heterocycles. In addition, taking into account the aforementioned versatility of these heterocycles, their reactivity is presented as well as their use as a ligand for metal complexes formation. Finally, those fused 1,5-naphthyridines that present biological activity and optical applications, among others, are indicated.Financial support from the Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI), Fondo Europeo de Desarrollo Regional (FEDER; RTI2018-101818-B-I00, UE), and by Gobierno Vasco, Universidad del País Vasco (GV, IT 992-16; UPV) is gratefully acknowledged

The role of the c-Jun N-terminal kinase (JNK) pathway in insulin resistance

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/103042Obesity is usually associated with a decreased response to insulin, a major metabolic defect known as insulin resistance and an early trait in the development of type 2 diabetes. The c-Jun N-terminal kinase (JNK) pathway has emerged as a central regulator of insulin sensitivity, locally and systemically, thereby, of body’s metabolic homeostasis. As the incidence of obesity and type 2 diabetes has alarmingly increased in the last few decades, there is a tremendous necessity to identify novel pharmacological targets to efficiently improve the therapeutic outcome. In this regard, the JNK pathway seems to meet most of the requirements for being an adequate candidate to direct pharmacological intervention

Gel-Free Tools for Quick and Simple Screening of Anti-Topoisomerase 1 Compounds

With the increasing need for effective compounds against cancer or pathogen-borne diseases, the development of new tools to investigate the enzymatic activity of biomarkers is necessary. Among these biomarkers are DNA topoisomerases, which are key enzymes that modify DNA and regulate DNA topology during cellular processes. Over the years, libraries of natural and synthetic small-molecule compounds have been extensively investigated as potential anti-cancer, anti-bacterial, or anti-parasitic drugs targeting topoisomerases. However, the current tools for measuring the potential inhibition of topoisomerase activity are time consuming and not easily adaptable outside specialized laboratories. Here, we present rolling circle amplification-based methods that provide fast and easy readouts for screening of compounds against type 1 topoisomerases. Specific assays for the investigation of the potential inhibition of eukaryotic, viral, or bacterial type 1 topoisomerase activity were developed, using human topoisomerase 1, Leishmania donovani topoisomerase 1, monkeypox virus topoisomerase 1, and Mycobacterium smegmatis topoisomerase 1 as model enzymes. The presented tools proved to be sensitive and directly quantitative, paving the way for new diagnostic and drug screening protocols in research and clinical settings.This research was funded in part by the Ministerio de Ciencia e Innovación, Spain (PID2021-122558OB-I00, UE) and by Gobierno Vasco, Universidad del País Vasco (GV, IT1701-22; UPV)

In vitro and in vivo activity of a new small-molecule inhibitor of HDAC6 in mantle cell lymphoma

Cancer origin and development is associated not only with genetic alterations, but also with the disturbance of epigenetic profiles.1 In this regard, the tumoral epigenome is characterized by both specific and general shifts in the DNA methylation and histone-modification landscapes.1 However, in contrast to genetic disruption, the effect of epigenetic modifications or marks may potentially be reversed by the use of drugs that target enzymes involved in adding, removing or signaling DNA methylation and histone modifications.1 This basic knowledge has been adopted into clinical practice, and inhibitors of histone deacetylases and DNA demethylating agents have been approved for use in the therapy of hematologic malignancies, such as cutaneous T-cell lymphoma and myelodysplastic syndrome, respectively.2 Other promising epigenetic drugs include inhibitors of histone methyltransferases,2 histone demethylases,2 histone kinases,3 and bromodomain proteins that interfere with the 'reading' of acetylated histone residues

Fused 1,5-Naphthyridines: Synthetic Tools and Applications

Heterocyclic nitrogen compounds, including fused 1,5-naphthyridines, have versatile applications in the fields of synthetic organic chemistry and play an important role in the field of medicinal chemistry, as many of them have a wide range of biological activities. In this review, a wide range of synthetic protocols for the construction of this scaffold are presented. For example, Friedländer, Skraup, Semmlere-Wolff, and hetero-Diels-Alder, among others, are well known classical synthetic protocols used for the construction of the main 1,5-naphthyridine scaffold. These syntheses are classified according to the nature of the cycle fused to the 1,5-naphthyridine ring: carbocycles, nitrogen heterocycles, oxygen heterocycles, and sulphur heterocycles. In addition, taking into account the aforementioned versatility of these heterocycles, their reactivity is presented as well as their use as a ligand for metal complexes formation. Finally, those fused 1,5-naphthyridines that present biological activity and optical applications, among others, are indicated

The role of the c-Jun N-terminal kinase (JNK) pathway in insulin resistance

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/103042Obesity is usually associated with a decreased response to insulin, a major metabolic defect known as insulin resistance and an early trait in the development of type 2 diabetes. The c-Jun N-terminal kinase (JNK) pathway has emerged as a central regulator of insulin sensitivity, locally and systemically, thereby, of body’s metabolic homeostasis. As the incidence of obesity and type 2 diabetes has alarmingly increased in the last few decades, there is a tremendous necessity to identify novel pharmacological targets to efficiently improve the therapeutic outcome. In this regard, the JNK pathway seems to meet most of the requirements for being an adequate candidate to direct pharmacological intervention

La bandera de Santa Eulàlia: un tractament de conservació integral

El Museu d’Història de Barcelona (MUHBA) ha desplegat el projecte de conservació-restauració de la bandera de Santa Eulàlia. Per això ha estat necessari resseguir la història i les vicissituds d’aquesta peça tan emblemàtica per a la ciutat de Barcelona, estudiar-ne les característiques materials i els entorns als quals ha estat sotmesa així com avaluar les seves successives mutacions. Això ha permès dissenyar l’estratègia adequada de conservació i restauració pensada perquè sigui efectiva a llarg termini. Per assolir-ho s’ha conformat un equip de treball amb especialistes de diverses branques de la restauració i amb el concurs de diverses disciplines. La peça actualment està exposada al Born Centre Cultural (Barcelona)